This project is designed to study genetic and immunologic factors involved in BCG-induced chronic granulomatous pulmonary inflammation and splenomegaly. Studies already performed indicate that the capacity to develop pulmonary inflammation and splenomegaly is restricted to certain inbred strains of mice and not controlled by genes within the H-2 complex. We are extending these studies to determine the number of genes involved in responsiveness by performing breeding studies in F1 x nonresponder and F1 x F1 mice, as well as studying recombinant-inbred (RI) mice. In addition, experiments have been designed to determine linkage to other genetic markers using RI mice and selected inbred strains for linkage analysis. These studies are related to diseases in man, such as sarcoidosis, hypersensitivity pneumonitis, tuberculosis and coccidioidomycosis, all of which involve granulomatous inflammation and may be associated with genetic control. This project is also designed to study the immunologic basis of BCG-induced chronic pulmonary inflammation and its possible modulation by suppressor cells and factors. We are now testing the possibility that BCG-induced pulmonary inflammation is a manifestation of cellular immunity by evaluating the development of pulmonary lesions in T cell deficient responder mice ("B" and nude mice). Furthermore, we have observed that the enlarged spleens of responder mice contain adherent, non-T cells which suppress mitogen, antibody, and cell-mediated responses. The possible role of these cells in modulating BCG-induced pulmonary inflammation is being evaluated. Adherent suppressor cells have been described in several experimental animal systems as well as in a few human diseases such as sarcoidosis and tuberculosis. Continued investigation of these cells in animal models may provide clues to their function in man.